1. Field of the Invention
The present invention relates generally to the fields of immunology and molecular biology. Specifically, the present invention identifies molecular classifiers of hyperreactivity, which will allow rapid identification of individuals with asthma. This rapid identification will help clinical investigation on the etiology and intervention for asthma.
2. Description of the Related Art
Asthma is a chronic inflammatory disease of the airways characterized by recurrent episodes of symptomical airflow obstruction and various degrees of airways hyperreactivity to nonspecific stimuli (Busse and Lemanske, 2001). The recognition that this disease has a chronic inflammatory component has directed therapy towards early use of inhaled glucocorticoid therapy, typically producing significant reductions in inflammatory markers, and improvement in pulmonary function (Busse and Lemanske, 2001). However, there is a subset of patients (˜5-7%) with “severe”, or “refractory” asthma that do not respond to glucocorticoids. These patients account for 40-50% of the health costs of asthma, and incur significant morbidity and decrements in quality of life (Godard et al., 2002; Serra-Battles, 1998).
Severe asthma is a heterogeneous disorder with distinct ages of onset, duration of disease, degree of airflow impairment, presence of modifying factors (GERD, sinusitis), and type of underlying inflammation (Moore and Peters, 2006; Wenzel et al., 1999). In this regard, phenotypic analysis of severe asthmatics prospectively enrolled in the Severe Asthma Research Program (SARP) has shown that severe asthmatics tend to be older and have a greater frequency of respiratory infection (sinusitis and/or pneumonia), suggesting that as a group, they have alterations in innate immune defenses (Moore et al., 2007). Additionally, at least some severe asthmatics have been characterized as having either neutrophil-predominant inflammation, or increased tissue eosinophils by endobronchial biopsy (Wenzel, 2003; Jatakanon et al., 1999). These latter patients have been shown to increase near-fatal events, especially those with early onset disease, and are associated chronic airway remodeling, indicated by increased sub-basement membrane thickening (Wenzel et al., 1999). However, others have found no clinical differences between the eosinophilic and noneosinophilic phenotypes (Lemiere et al., 2006). Together, these observations suggest that severe asthma is a pathologically heterogenous disorder that still lacks an objective method for distinguishing clinically significant subtypes.
Thus, prior art in diagnostic assays that will allow medical personnel to rapidly identify individuals who may benefit from more intensive treatment of their asthma, thereby reducing morbidity and improving quality of life for those affected. The present invention full fills this long-standing need and desire in the art.